Herpes simplex virus acyclovir

Novel isosteres 545 of the antiviral agent acyclovir were synthesized in three stages (84JHC697) by dehydrative coupling of 3-amino-6-aminomethyl[ 1,2,4]triazin-5-(4//)-one with 2-(benzoyloxy)ethoxyacetic acid to give the respective amide that cyclized and deprotected to give 545. It showed no activity against herpes simplex virus types I and II in cell culture (Scheme 112). 

Catechins and proanthocyanidins have a documented antiviral activity. Catechins from an extract of Cocos nucifera husk fibre exhibited a strong inhibitory activity against acyclovir-resistant herpes simplex virus type 1 (HSV-l-ACVr) [62]. The use of 10 to 20ngml of ECG and EGCG has been reported to cause 50% inhibition of human immunodeficiency virus reverse transcriptase [89], while Kara and Nakayama [90] reported that a patented chewing gum containing tea catechins is claimed to prevent viral infections against influenza and to inhibit dissemination of this virus. 

YT Bryson, M Dillon, G Acuna, S Taylor, JD Cherry, BL Johnson, E Wiesmeier, W Growden, T Greagh-Kirk, R Keeney. Treatment of first episodes of genital herpes simplex virus infection with oral acyclovir. A randomized double-blind controlled trial in normal subjects. N Engl J Med 308 916-921, 1983. 

Herpes simplex virus (HSV) /nfecf/ons Treatment of acyclovir-resistant mucocutaneous HSV infections in immunocompromised patients. 

Pharmacology Valacyclovir is the hydrochloride salt of L-valyl ester of the antiviral drug acyclovir. Valacyclovir is rapidly converted to acyclovir, which has in vitro and in vivo inhibitory activity against herpes simplex virus types I (HSV-1) and II (HSV-2), and varicella-zoster virus (VZV). In cell culture, acyclovir has the highest antiviral activity against HSV-1, followed by (in decreasing order of potency) HSV-2 and VZV. In vitro, acyclovir triphosphate stops replication of herpes viral DMA in 3 ways 1) Competitive inhibition of viral DMA polymerase 2) incorporation and termination of... 

Unlabeled Uses Treatment of acyclovir-resistant herpes simplex virus, adenovirus, foscarnet-resistant CMV, ganciclovir-resistant CMV, varicella-zoster virus... 

Mechanism of Action Avirustatic antiviral that is converted to acyclovir triphosphate, becoming part of the viral DNA chain. Therapeutic Effect Interferes with DNA synthesis and replication of herpes simplex virus and varicella-zoster virus. Pharmacokinetics Rapidly absorbed after PO administration. Protein binding 13%-18%. Rapidly converted by hydrolysis to the active compound acyclovir. Widely distributed to tissues and body fluids (including cerebrospinal fluid CSF ). Primarily eliminated in urine. Removed by hemodialysis. Half-life 2.5-3.3 hr (increased in impaired renal function). 

For example, acyclovir with TI — 10 against herpes simplex virus is safer or more selective [9] than its derivative, ganciclovir (TI = 2-3 against cytomegalovirus) [10]. 

Topical acyclovir (Zovirax) is available as a 5% ointment topical penciclovir (Denavir), as a 1% cream for the treatment of recurrent orolabial herpes simplex virus infection in immunocompetent adults. Adverse local reactions to acyclovir and penciclovir may include pruritus and mild pain with transient stinging or burning. 

Note Herpes simplex virus encodes a virus-specific thymidine. kinase, which phosphorylates the nucleoside analog acyclovir (acycloguanosine) to form acycloguanosine monophosphate. After further phosphorylation, the resulting acycloguanosine triphosphate is incorporated by the viral DNA polymerase into viral DNA, causing chain termination in virus-infected cells.]... 

Acyclovir is useful in the treatment of herpes. Oral herpes is caused by the herpes simplex virus 1 (HSV-1), and genital herpes is caused by the herpes simplex virus 2 (HSV-2). More than 90 percent of the world s population is infected with the oral herpes virus, though there are many infected people who do not exhibit symptoms. Genital herpes is the most prevalent nondurable sexually transmitted disease. In the United States, there are about 30 million people infected with HSV-2 and an estimated 200,000 to 500,000 new cases each year. 

Soyasaponin I and II were studied in vitro against herpes simplex virus type I (HSV-1). Soyasaponin II was more potent than soyasaponin I in the reduction of HSV-1 production. Soyasaponin II was also found to inhibit the replication of human cytomegalovirus, influenza virus, and human immunodeficiency virus type 1. This activity was not due to the inhibition of virus penetration and protein synthesis, but might involve a virucidal effect. When acyclovir and soyasaponin II were evaluated in combination for anti-HSV-1 activity, additive antiviral effects were observed for this virus [160]. Astragaloside II afforded almost 100% protection of T-lymphocytes in vitro against the cytophatic effects of HIV infection. However, the EC50 of ca. 2.5 x 105 molar was difficult to achieve in vivo [98],... 

In a recent investigation of phenolic compounds tested, using herpes simplex virus type 1 (HSV-1) infected Vero cells, caffeic acid has been reported to inhibit virus replication [91], In a related study [92], chlorogenic acid significantly inhibited acyclovir-resistant HSV-1 replication without any cytotoxicity. However, flavonoids have exhibited cytotoxicity at the same concentration [92],... 

Topical acyclovir (Zovirax) is available as a 5% ointment for application to primary cutaneous herpes simplex infections and to limited mucocutaneous herpes simplex virus infections in immunocompromised patients. In primary infections, the use of topical acyclovir shortens the duration of viral shedding and may decrease healing time. In localized, limited mucocutaneous infections in immunocompromised patients, its use may be associated with a decrease in the duration of viral shedding. 

Other notable research by Elion led to the development of the antiviral drug Acyclovir (acycloguanosine), which has been used to treat the herpes simplex viruses. Her studies during the 1970s showed that Acyclovir inhibited viral replication by interfering with viral DNA synthesis. The sub-... 

Vidarabine [vye DARE a been] arabinofuranosyl adenine, ara-A, adenine arabinoside) is one of the most effective of the nucleoside analogs and is also the least toxic. However, it has been supplanted clinically by acyclovir, which is more efficacious and safe. Although vidarabine is active against herpes simplex virus type 1 (HSV-1), HSV-2, and varicella-zoster virus (VZV), its use is limited to treatment of immunocompromised patients with herpes simplex keratitis or encephalitis, or VZV infections. Vidarabine, an adenosine analog, is converted in the cell to its 5 -triphosphate analog (ara-ATP), which is postulated to inhibit viral DNA synthesis. Some resistant herpes virus... 

Penciclovir [pen SIK lo veer] is an acyclic guanosine nucleoside derivative that is active against herpes simplex virus Types I and II, and against varicella-zoster virus. Penciclovir is only administered topically (Figure 37.8). Penciclovir is monophosphorylated by viral thymidine kinase, and cellular enzymes form the nucleoside triphosphate, which inhibits herpes DNA polymerase. Penciclovir triphosphate has an intracellular half-life 20 to 30 times longer than does acyclovir triphosphate (see p. 365). Penciclovir is negligibly absorbed from topical application, and is well tolerated. Both healing and pain are shortened approximately one-half day in duration, compared to placebo-treated subjects. 

Acyclovir is a potent inhibitory of viruses of the herpes group, particularly herpes simplex virus (HSV I and II) and herpes zoster varicella virus. Unfortunately, acyclovir has a short half-life (2-3 h), and the oral dosage form must be taken five times daily, which is very inconvenient for patients [75,76], Consequently, the aim of this study was to develop a controlled-release formulation of acyclovir that could be taken twice daily. The materials used to prepare the tablets were acyclovir (Kern Pharma, Tarrasa, Barcelona) and hydroxypropyl methylcellulose (Methocel K4M) (Colorcon) a hydrophilic cellulose derivative as the matrix-forming material. 

Fife KH, et al. Valaciclovir versus acyclovir in the treatment of first-episode genital herpes infection. Results of an international, multicenter, double-blind, randomized clinical trial. The Valaciclovir International Herpes Simplex Virus Smdy Group. SexTransm Dis 1997 24(8) 481-486. 

Malvy D, TreRhaud M, Boues S, et al. A retrospective, case-control smdy of acyclovir resistance in herpes simplex virus. Clin Infect Dis 2005 41(3) 320-326. 

Shin YK, Cai G, Weinberg A, et al. Frequency of acyclovir-resistant herpes simplex virus in clinical specimens and laboratory isolates. J Chn Microbiol 2001 39(3) 913-917. 

Herpetic Eye Disease Study Group. Oral acyclovir for herpes simplex virus eye disease effect on prevention of epithelial keratitis and stromal keratitis. Arch Ophthalmol 2000 118 1030-1036. 

Uchoa UBC, Rezende RH, Carrasco MA, et al. Long-term acyclovir use to prevent recurrent ocular herpes simplex virus infection.Arch Ophthalmol 2003 121 1702-1704. 

Some fatty acids, especially unsaturated fatty acids, are well-known skin penetration enhancers. It is also known that many fatty acids possess antimicrobial activity. The topical activity of the anti-viral drug acyclovir is hampered by its inadequate permeability through the skin barrier. Some reports have shown that fatty acid extract of cod liver oil as well as the extract in the form of an ointment show effective antiviral properties against herpes simplex virus (HSV-1) (37). 

Foscamet is used for the treatment of cytomegalovirus (CMV) retinitis and mucocutaneous acyclovir-resistant herpes simplex virus (HSV) infections. It may also be beneficial in other types of CMV or HSV infections (Wagstaff and Bryson, 1994). 

Klein, N.A., Mabie, W.C., Shaver, D.C., Latham, P.S., Adamec, T.A., Pinstein, M.L., Riely, C.A. Herpes simplex virus hepatitis in pregnancy. Two patients successfully treated with acyclovir. Gastroenterology 1991 100 239 - 244... 

Keywords Encephalitis Herpes simplex virus type 1 Varicella zoster virus Cytomegalovirus West Nile virus Acyclovir Valacyclovir Ganciclovir Cidofovir Famciclovir Foscamet Latencyneurological disorders Fifecycle... 

Erlich KS, Mills J, Chatis P, Mertz GJ, Busch DF, Follansbee SE, Grant RM, Crumpacker CS. Acyclovir-resistant Herpes simplex virus infections in patients with the acquired immunodeficiency syndrome. N Engl J Med 1989 320(5) 293-6. 

Straus SE, Smith HA, Brickman C, de Miranda P, McLaren C, Keeney RE. Acyclovir for chronic mucocutaneous Herpes simplex virus infection in immunosuppressed patients. Ann Intern Med 1982 96(3) 270-7. 

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